Low-frequency and low-intensity ultrasound-mediated microvessel disruption enhance the effects of radiofrequency ablation on prostate cancer xenografts in nude mice

Yang,Yu; Bai,Wenkun; Chen,Yini; Zhang,Wei; Wang,Meiwen; Hu,Bing

doi:10.3892/mmr.2015.4375

Low-frequency and low-intensity ultrasound-mediated microvessel disruption enhance the effects of radiofrequency ablation on prostate cancer xenografts in nude mice

Authors:
- Yu Yang
- Wenkun Bai
- Yini Chen
- Wei Zhang
- Meiwen Wang
- Bing Hu
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Affiliations: Department of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Institute of Ultrasound in Medicine, Shanghai 200233, P.R. China
Published online on: September 28, 2015 https://doi.org/10.3892/mmr.2015.4375
Pages: 7517-7525

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Abstract

The aim of the present study was to examine the impact of low-frequency, low-intensity ultrasound (US)-stimulated microbubbles (USMB) on radiofrequency ablation (RFA) in the treatment of nude mice with human prostate cancer xenografts. The tumor‑bearing nude mice were divided into three groups: The USMB+RFA group was treated with USMB immediately followed by RFA, the RFA group was treated with RFA alone, and the control group remained untreated. The animals underwent enhanced US to calculate the tumor volumes, ablation volumes and ablation rates. Subsequently, the tumors were excised for hematoxylin and eosin staining, to identify necrosis in the tumors following the treatments, and immunohistochemical staining, to analyze the apoptotic index (AI), proliferative index (PI) and microvessel density (MVD) at 1, 4 and 7 days post-treatment. Each group contained five mice at each time‑point. Necrosis was apparent in the center of the tumors in the treatment groups. Ablation lesion volumes of the USMB+RFA group were larger than those in the RFA group at 1 and 4 days post‑treatment (P=0.002 and P=0.022, respectively), and the ablation rates of the USMB+RFA group were significantly higher, compared with the RFA group at the three time‑points (all P<0.001). There were fewer apoptotic cells and more proliferative cells in the RFA group, compared with the control group 1,4 and 7 days post‑treatment (all P<0.05). The AI of the USMB+RFA group was higher than that of the control group and lower than that of the RFA group 1 day post-treatment (P=0.034 and P=0.016, respectively). The PI of the USMB+RFA group was lower than that of the control group and higher than that of the RFA group 4 and 7 days post-treatment (all P<0.05). No significant differences were observed in MVD among the three groups throughout the experiment. In conclusion, exposure to USMB prior to RFA produced larger volumes of ablation, compared with treatment with RFA alone, and increased AI and reduced PI in the residual carcinoma cells induced by RFA.

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